scholarly journals Dorsal Bed Nucleus of the Stria Terminalis-Subcortical Output Circuits Encode Positive Bias in Pavlovian Fear and Reward

2021 ◽  
Vol 15 ◽  
Author(s):  
Nadia Kaouane ◽  
Sibel Ada ◽  
Marlene Hausleitner ◽  
Wulf Haubensak
Keyword(s):  
Calcium Imaging ◽  
Affective Response ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Addictive Behaviors ◽  
Bed Nucleus ◽  
Reward Seeking ◽  
Reward Conditioning ◽  
Neuronal Output ◽  
Deep Brain

Opposite emotions like fear and reward states often utilize the same brain regions. The bed nucleus of the stria terminalis (BNST) comprises one hub for processing fear and reward processes. However, it remains unknown how dorsal BNST (dBNST) circuits process these antagonistic behaviors. Here, we exploited a combined Pavlovian fear and reward conditioning task that exposed mice to conditioned tone stimuli (CS)s, either paired with sucrose delivery or footshock unconditioned stimuli (US). Pharmacological inactivation identified the dorsal BNST as a crucial element for both fear and reward behavior. Deep brain calcium imaging revealed opposite roles of two distinct dBNST neuronal output pathways to the periaqueductal gray (PAG) or paraventricular hypothalamus (PVH). dBNST neural activity profiles differentially process valence and Pavlovian behavior components: dBNST-PAG neurons encode fear CS, whereas dBNST-PVH neurons encode reward responding. Optogenetic activation of BNST-PVH neurons increased reward seeking, whereas dBNST-PAG neurons attenuated freezing. Thus, dBNST-PVH or dBNST-PAG circuitry encodes oppositely valenced fear and reward states, while simultaneously triggering an overall positive affective response bias (increased reward seeking while reducing fear responses). We speculate that this mechanism amplifies reward responding and suppresses fear responses linked to BNST dysfunction in stress and addictive behaviors.

scholarly journals A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip E. Mosley ◽  
François Windels ◽  
John Morris ◽  
Terry Coyne ◽  
Rodney Marsh ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Adverse Events ◽  
Brain Stimulation ◽  
Stria Terminalis ◽  
Treatment Resistant ◽  
Obsessive Compulsive ◽  
Double Blind ◽  
Bed Nucleus ◽  
Compulsive Disorder ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

scholarly journals Deep Brain Stimulation as a Treatment Approach for Anorexia Nervosa: a Systematic Literature Review

2019 ◽  
Vol 38 (03) ◽  
pp. 175-182 ◽  
Author(s):  
Ledismar José da Silva ◽  
Tâmara Husein Naciff ◽  
Maria Flávia Vaz de Oliveira
Keyword(s):  
Anorexia Nervosa ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Anterior Cingulate ◽  
Stria Terminalis ◽  
Electrode Implantation ◽  
Bed Nucleus ◽  
Negative Impacts ◽  
Deep Brain

AbstractAnorexia nervosa is a psychiatric disorder characterized by distortions of body size, weight, and shape perception, as well as by food restriction and/or binge and purging behaviors. It mostly affects young women and causes severe negative impacts on their physical, psychological, and social health. Recent studies have analyzed deep brain stimulation (DBS), a neurosurgical procedure that involves electrode implantation in strategical brain areas, to obtain remission of the symptoms of anorexia nervosa. The results showed that the stimulation of areas associated to the neurocircuitry of anorexia nervosa, such as nucleus accumbens, anterior cingulate cortex, ventral striatum, and bed nucleus of the stria terminalis, provokes beneficial responses in terms of body mass index, quality of life, social functioning, and psychiatric comorbidities. Nevertheless, broader investigations are needed to endorse the clinical usage of DBS in the management of anorexia nervosa.

scholarly journals Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum

2008 ◽  
Vol 32 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Christopher M. Olsen ◽  
Yong Huang ◽  
Shirlean Goodwin ◽  
Daniel C. Ciobanu ◽  
Lu Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Insight Into

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.

scholarly journals Quantitative Analysis of 1300-nm Three-photon Calcium Imaging in the Mouse Brain

2019 ◽  
Author(s):  
Tianyu Wang ◽  
Chunyan Wu ◽  
Dimitre G. Ouzounov ◽  
Wenchao Gu ◽  
Fei Xia ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Large Scale ◽  
Brain Regions ◽  
Excitation Power ◽  
Excitation Pulse ◽  
Two Photon ◽  
Tissue Heating ◽  
Photon Count ◽  
Photon Excitation ◽  
Deep Brain

Abstract1300-nm three-photon calcium imaging has emerged as a useful technique to allow calcium imaging in deep brain regions. Application to large-scale neural activity imaging entails a careful balance between recording fidelity and tissue heating. We calculated and experimentally verified the excitation pulse energy to achieve the minimum photon count required for the detection of calcium transients in GCaMP6s-expressing neurons for 920-nm two-photon and 1320-nm three-photon excitation, respectively. Brain tissue heating by continuous three-photon imaging was simulated with Monte Carlo method and experimentally validated with immunohistochemistry. We observed increased immunoreactivity with 150 mW excitation power at 1.0- and 1.2-mm imaging depths. Based on the data, we explained how three-photon excitation achieves better calcium imaging fidelity than two-photon excitation in the deep brain and quantified the imaging depth where three-photon microscopy should be applied. Our analysis presents a translatable model for the optimization of three-photon calcium imaging based on experimentally tractable parameters.

scholarly journals Quantitative analysis of 1300-nm three-photon calcium imaging in the mouse brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tianyu Wang ◽  
Chunyan Wu ◽  
Dimitre G Ouzounov ◽  
Wenchao Gu ◽  
Fei Xia ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Large Scale ◽  
Brain Regions ◽  
Excitation Power ◽  
Signal Attenuation ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Tissue Heating ◽  
Photon Excitation ◽  
Deep Brain

1300 nm three-photon calcium imaging has emerged as a useful technique to allow calcium imaging in deep brain regions. Application to large-scale neural activity imaging entails a careful balance between recording fidelity and perturbation to the sample. We calculated and experimentally verified the excitation pulse energy to achieve the minimum photon count required for the detection of calcium transients in GCaMP6s-expressing neurons for 920 nm two-photon and 1320 nm three-photon excitation. By considering the combined effects of in-focus signal attenuation and out-of-focus background generation, we quantified the cross-over depth beyond which three-photon microscopy outpeforms two-photon microscopy in recording fidelity. Brain tissue heating by continuous three-photon imaging was simulated with Monte Carlo method and experimentally validated with immunohistochemistry. Increased immunoreactivity was observed with 150 mW excitation power at 1 and 1.2 mm imaging depths. Our analysis presents a translatable model for the optimization of three-photon calcium imaging based on experimentally tractable parameters.

scholarly journals A Randomised, Double-Blind, Sham-Controlled Trial of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis for Treatment-Resistant Obsessive-Compulsive Disorder

2020 ◽  
Author(s):  
Philip E. Mosley ◽  
François Windels ◽  
John Morris ◽  
Terry Coyne ◽  
Rodney Marsh ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Adverse Events ◽  
Brain Stimulation ◽  
Stria Terminalis ◽  
Treatment Resistant ◽  
Obsessive Compulsive ◽  
Double Blind ◽  
Bed Nucleus ◽  
Compulsive Disorder ◽  
Deep Brain

1ABSTRACTDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ±1.9 points (Χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ±3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

scholarly journals Orexin A role in mechanisms of reinforcement in the bed nucleus of stria terminalis

2015 ◽  
Vol 13 (2) ◽  
pp. 20-26
Author(s):  
Andrei Andreevich Lebedev ◽  
Eugeny Grigorievich Shumilov ◽  
Eugeny Rudolfovich Bychkov ◽  
Vitaly Ivanovich Morozov ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Lateral Hypothalamus ◽  
Behavioral Sensitization ◽  
Brain Regions ◽  
Brain Stimulation Reward ◽  
Stria Terminalis ◽  
Self Administration ◽  
Orexin A ◽  
Drug Reinforcement ◽  
Bed Nucleus ◽  
Self Stimulation

The orexin family of hypothalamic neuropeptides has been implicated in reinforcement mechanisms relevant to both food and drug reward. Previous behavioral studies with antagonists at the orexin A-selective receptor OX(1), have demonstrated its involvement in behavioral sensitization, conditioned place-preference, self-administration and reinstatement of drugs abuse. There are dense concentrations of hypocretin receptors, in brain regions implicated in drug reinforcement processes, such as the nucleus accumbens, ventral tegmental area and bed nucleus of the stria terminalis Adult male Wistar rats were implanted the stimulating electrodes to the lateral hypothalamus. Simultaneously, the microcanules were implanted into the BNST to inject the OX(1) receptor antagonist. Rats were trained to perform intracranial self-stimulation. The effects of the OX(1)-selective antagonist SB-408124 on brain stimulation-reward (BSR) were measured. SB-408124 injected into the BNST (1µg/1 µl in volume for each injection.) alone had no effect on self-stimulation of lateral hypothalamus. Amphetamine (1 mg/kg i.p.) potentiated BSR, measured as lowering of BSR threshold and enhancing of BSR frequency. Amphetamine-induced stimulatory effects on intracranial self-stimulation was blocked by injections of SB-408124 into BNST. These data demonstrate that OX(1) play an important role in regulating the reinforcing and reward-enhancing properties of amphetamine and suggest that orexin transmission is likely essential for establishing and maintaining the amphetamine habit in human addicts. However, the observations that OX1 antagonism reduce brain reward and block stress- and cue-induced reinstatement of drug-seeking suggests that this class of compounds may be useful additions to stress-reduction and other behavioral therapies in the treatment of substance abuse disorders.

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